Localization and characterization of meperidine esterase of rats.

Abstract

Meperidine esterase of the rat was studied. The enzyme activity was found in the liver microsomes but not in brain tissue or blood. The enzyme had an optimal activity between pH 8.0 to 9.5 and a temperature of 53 degrees-55 degrees C. The heat of activation was found to be 4.6 X 10(6) cal/mol and the KM 1.2 X 10(-4) M. The esterase activity of older male rats (200-350 g) was significantly higher than that of the younger group (150-175 g). There was no significant difference in specific activity of hepatic meperidine esterase between male and female rats, and between rats fasted for 20 hr and phenobarbital- and benzopyrene-treated rats and their respective control groups. However, the liver weight and the microsomal protein yield per g of liver of fasted rats were significantly smaller, and those of phenobarbital- and benzopyrene-treated rats were significantly larger, than those of the control group. The overall enzyme activity per liver of phenobarbital- and of benzopyrene-treated rats was therefore significantly increased. The specific enzyme activities in microsomes prepared by ultracentrifugation and by calcium aggregation were not significantly different, although the ultracentrifugation method resulted in a higher yield of hepatic microsomal protein. The enzyme activities in microsomes prepared by ultracentrifugation/or calcium aggregation and frozen at -20 degrees C up to 22 days were not significantly different from those of freshly prepared microsomes. The enzymatic activity was inhibited by cocaine hydrochloride, isocarboxazid, neostigmine methyl sulfate, alpha-naphthyl acetate, p-nitrophenyl acetate, paraoxon, propoxyphene hydrochloride, phenelzine sulfate, physostigmine sulfate, SKF 525-A, tranylcypromine sulfate, fluoride ions, methanol, and ethanol.